Inflammation-induced reversible switch of the neuron-specific enolase promoter from Purkinje neurons to Bergmann glia.
Inflammation-induced reversible switch of the neuron-specific enolase promoter from Purkinje neurons to Bergmann glia.
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DOI：
10.1038/srep27758
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发表时间：
2016-06-13
影响因子：
4.6
通讯作者：
Hirai H
中科院分区：
文献类型：
--
作者：
Sawada Y;Konno A;Nagaoka J;Hirai H
神经元特异性烯醇化酶（NSE）是在成熟神经元和神经元起源的细胞中发现的糖酵解同工酶。将携带NSE启动子的9型腺相关病毒（AAV 9）载体注射到小脑皮质中可能引起神经元细胞（如浦肯野细胞（PC）和中间神经元）的特异性转导，但不引起Bergmann胶质细胞（BG）的特异性转导。然而，我们发现BG主导的转导没有PC转导沿着用于病毒注射的创伤性针道。通过脂多糖（LPS）与AAV 9的共同应用的神经炎症的增强显著扩大了BG占优势的区域，同时增强了小胶质细胞活化。随着神经炎症的消退，BG主导的转导逐渐被PC主导的转导所取代。使用神经胶质瘤细胞培养物的实验揭示了由于葡萄糖剥夺导致的NSE启动子的显著活化，表明细胞内储存的糖原通过糖酵解途径代谢以获得能量。BG中糖酵解酶启动子的激活与PC中的失活同时进行，可能对激活BG中乳酸的产生和乳酸的利用具有病理生理学意义，乳酸是由BG-PC乳酸穿梭提供的，作为受损PC中的主要能量来源。
Neuron-specific enolase (NSE) is a glycolytic isoenzyme found in mature neurons and cells of neuronal origin. Injecting adeno-associated virus serotype 9 (AAV9) vectors carrying the NSE promoter into the cerebellar cortex is likely to cause the specific transduction of neuronal cells, such as Purkinje cells (PCs) and interneurons, but not Bergmann glia (BG). However, we found BG-predominant transduction without PC transduction along a traumatic needle tract for viral injection. The enhancement of neuroinflammation by the co-application of lipopolysaccharide (LPS) with AAV9 significantly expanded the BG-predominant area concurrently with the potentiated microglial activation. The BG-predominant transduction was gradually replaced by the PC-predominant transduction as the neuroinflammation dissipated. Experiments using glioma cell cultures revealed significant activation of the NSE promoter due to glucose deprivation, suggesting that intracellularly stored glycogen is metabolized through the glycolytic pathway for energy. Activation of the glycolytic enzyme promoter in BG concurrently with inactivation in PC may have pathophysiological significance for the production of lactate in activated BG and the utilization of lactate, which is provided by the BG-PC lactate shuttle, as a primary energy resource in injured PCs.
影响因子：
3
作者：
Nagykery, Nicholas;Terwilliger, Ernest F.;Geula, Changiz
通讯作者：
Geula, Changiz